Located in the westernmost IDeA-eligible state in the middle of the Pacific Ocean, approximately 4,000 km from North America and the major island nations of Oceania, the University of Hawaii at Manoa (UH-Manoa) is strategically positioned to monitor the emergence and spread of newly recognized and reemerging infectious diseases, by virtue of its geographic proximity and strong ties to institutions in the Asia-Pacific region. COBRE funding during the initial five-year period has allowed the establishment of the Pacific Center for Emerging Infectious Diseases Research, a multidisciplinary center of excellence for research and training on new, emerging and re-emerging microbial threats of regional concern and global importance. Renewed COBRE funding is being requested to strengthen and transform the COBRE Center into a translational science center of excellence for developing improved diagnostics, therapeutics and interventions for emerging infectious diseases. The relocation of COBRE activities into state-of-the-art laboratory space in a newly constructed, State-financed 200,000-square-foot BioSciences Building has exacted a sea change by creating an academic home for infectious diseases research at UH-Manoa. The current grant period has witnessed mainstream funding of approximately $17.5 million for non-HIV/AIDS infectious diseases research and training, far exceeding original expectations. In this competitive continuation resubmission, four promising junior and mid-career faculty have been selected for COBRE support to conduct hypothesis-driven research projects that have been rated as excellent to outstanding with a high likelihood of extramural funding. Importantly, strong leadership and dedicated Mentors, Collaborators and External Advisors have been identified, and complementary technical cores in Bioinformatics, BSL-3/ABSL-3 Biocontainment and Molecular and Cellular Immunology will be enhanced, to ensure that the COBRE Investigators achieve research independence during the grant period. Furthermore, an institutional commitment to recruit four additional tenure-track faculty in tropical infectious diseases and to subsidize core facilities will help to solidify the critical mass of investigators for this high-priority research area, as well as to sustain this multidisciplinary center for UH-Manoa and the State of Hawaii during and beyond the new grant period.